Radium-223 Remains Effective Following AR Inhibition in CRPC

Published Online: 11:56 AM, Tue June 16, 2015

Neal D. Shore, MD

The efficacy of radium-223 (Xofigo) was not impacted by prior treatment with an androgen receptor inhibitor for men with bone metastatic castration-resistant prostate cancer (CRPC), according to an analysis authored by Neal D. Shore, MD, from the 2015 AUA Annual Meeting showed.

“In this extended access program, radium-223 was safe and well tolerated, regardless of prior or concurrent exposure to abiraterone and/or enzalutamide,” Shore, director of Carolina Urologic Research Center in Myrtle Beach, South Carolina, and colleagues concluded in a poster presentation. “Overall survival was comparable in radium-223-treated patients who received prior abiraterone and/or enzalutamide versus the overall extended-access population.”

The US expanded-access program for radium-223 was a prospective phase II, open-label, interventional trial for men with CRPC and bone metastases. The study was initiated to provide early access to radium-223 prior to regulatory approval.

Both abiraterone and enzalutamide were already available, and some men received one or both drugs before, during, and following the expanded-access program treatment period. Whether treatment with the newer hormonal therapies affected the safety or survival benefit of radium-223 was unclear.

Men enrolled in the expanded access program had an extensive treatment history. The data showed that 72% of men treated with abiraterone and 81% of men treated with enzalutamide also had received docetaxel. Men who received either of the hormonal therapies had higher alkaline phosphatase and prostate-specific antigen levels than did patients with no prior exposure to abiraterone or enzalutamide.

Men who received abiraterone and/or enzalutamide (n = 131) prior to radium-223 had a median overall survival (OS) of 15.6 months. The median OS was 15.6 months and 10.7 months for those treated with prior abiraterone (n = 120) and enzalutamide (n = 59), respectively. In the full population of the study (n = 184), the median OS was 17 months.

In those who received radium-223 with concurrent enzalutamide (n = 15), the median OS was 10.7 months. In the concurrent abiraterone arm (n = 25), the median OS was not estimable.

In patients in the abiraterone arm who were not treated with concurrent abiraterone (n = 159), the median OS was 15.6 months (similar to those treated with prior abiraterone). In patients who were not treated with concurrent enzalutamide (n = 169), the median OS was 17.1 months.

The 17 patients who received concurrent abiraterone and/or enzalutamide but had no prior treatment history of either hormonal therapy appeared to live longer, but the small numbers precluded definitive assessment, the authors wrote.

“Initial findings of overall survival in the small numbers of patients receiving concurrent abiraterone or enzalutamide are indeterminate," Shore said. “Current trials are under way to assess radium-223 combinations.”

In the small number of patients who received concurrent abiraterone or enzalutamide, radium-223 had a safety profile similar to that observed in the overall expanded-access population. The most common treatment-emergent grade 3/4 adverse events were anemia (16% with abiraterone, 13% with enzalutamide), thrombocytopenia (4%, 0%), and back pain (0%, 13%).

Grade 3/4 adverse events were apparent in 38% of those treated with prior abiraterone and 39% of those treated with prior enzalutamide. The rate of serious adverse events and treatment discontinuation was similar between the arms.

“Safety profiles of radium-223 were similar regardless of prior exposure to abiraterone or enzalutamide,” the authors noted. “The most common grade 3/4 events were anemia and thrombocytopenia.”
Shore ND, Vogelzang NJ, Fernandez D, et al. Radium-223 Dichloride in Expanded-Access Setting in the United States: Overall and Concurrent Experience With Abiraterone or Enzalutamide. Presented at: the: American Urological Association Annual Meeting; Tuesday, May 19, 2015; New Orleans, LA. Abstract: MP87-12.